title: Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency.
abstract: X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency.
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: taizo@staff.kanazawa-u.ac.jp.
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ohta
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Katoh
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.forename: Yozo
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Miyashita
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hamamoto
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Marsh
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000097:blood* / Q000276:immunology; D006801:Humans; D007223:Infant; D020382:Interleukin-18 / Q000097:blood*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood* / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000097:blood* / Q000276:immunology; D008297:Male; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
chemical_list: D020382:Interleukin-18; D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
keywords: AOSD; ATP; EBV; Epstein–Barr virus; FHL; HLH; Hemophagocytic lymphohistiocytosis (HLH); Interleukin-18; LPS; NK; NOD2; PBMCs; SAP; SLAM; SLAM-associated protein; X-linked inhibitor of apoptosis; X-linked inhibitor of apoptosis (XIAP); X-linked lymphoproliferative syndrome; X-linked lymphoproliferative syndrome (XLP); XIAP; XLP; adenosine triphosphate; adult-onset Still’s disease; familial hemophagocytic lymphohistiocytosis; hemophagocytic lymphohistiocytosis; lipopolysaccharide; natural killer; nucleotide-binding and oligomerization domain 2; peripheral blood mononuclear cells; sJIA; signaling lymphocyte activation molecule; systemic juvenile idiopathic arthritis